Brain damage as a result of hypoxia incurred during fetal or neonatal periods is now recognized as a major factor in neonatal mortality and as a cause of physiological and neurological deficits in the newborn. Although hypoxia has been ascribed to such factors as placental defects compression of the umbilical cord, toxemia and/or anemia, the mechanism(s) of hypoxic injury to the brain during the developmental period remain largely unknown. Equally little understood is the great variability in the degree of brain damage as a result of hypoxic exposure. The proposed study has three primary objectives: (1) To study, after different periods of hypoxic exposure imposed during the gestation and perinatal period, the gross abnormalities of the brain such as hemorrhage, herniation and hydrocephaly, and to record the incidence of aborted pregnancy following prenatal hypoxic injury. (2) To analyze biochemically the growth and maturation of the hypoxic brain in terms of several important parameters: nucleic acid content (as an index of cell number); protein and DNA ratios (as an index of cell size) and Cerebroside (as an index of myelination). (3) To study the cellular and histological organization, and the labelling index of the parietal cortex and the vermis of the cerebellum of the hypoxic brain. These studies will employ light and electron microscopy, and autoradiography. The experimental procedure for inducing hypoxia consists of exposing rats of dated pregnancy and newborn rats to low oxygen environments in an hypoxic chamber for varying periods of time. At selected intervals, the rats will be sacrificed and their brains used for biochemical and morphological studies. It is anticipated that the proposal will produce information which will shed light on how and to what extent hypoxia interferes with brain developement, and provide insight for the development of methods for prevention or amelioration.